This project focuses on the function of immune response (Ir) genes in the activation of thymus-derived (T)-lymphocytes, using a secondary proliferation assay. By a slope analysis of cell dose-response curves, we have shown that three different cells are involved in the proliferative response, a nonimmune antigen-presenting cell, and antigen specific, primed T lymphocyte, and a nonimmune, recruitable T lymphocyte. Experiments with radiation chimeras demonstrated that, of these three cell types, only the antigen-presenting cell has to posses high responder Ir genes. However, the proliferating, primed T lymphocyte must also have matured in a high responder environment. Studies of the proliferative response to the antigen, pigeon cytochrome c, demonstrated that two complementing Ir genes could control the response to a single antigenic determinant and that both gene products must be present in the same antigen-presenting cell in order to stimulate a response.